The potential of various cell organelles, which possess physical and genetic continuity, is known to play an important part in the overall differentiation of any eucaryote. Although the organelles cannot act independently, the very interdependence between the extra-nuclear and nuclear systems of the ever-changing and perpetuating interactions of the organelle activities with the nucleus are probably the essential cause of certain differentiation processes, since it is these cell organelles that affect some vital metabolic and other essential cellular processes in higher organisms. The biochemical basis of nucleus-organelle interaction(s) and its regulation during differentiation, however, remain virtually unexplored and poorly understood. Using the unicellular eucaryote Chlamydomonas in which mitosis, meiosis, gametic differentiation/de-differentiation and zygotic maturation/germination can be simply and accurately controlled, we plan to carry out basic studies to characterize the biochemical-physical nature of the nucleus-organelle interaction(s) and its causal relationship with normal differentiation at specific developmental stages. The consequence of abnormal nucleus-organelle interaction brought about either by nuclear/organelle mutation or by imposed artificial experimental conditions in embryological or zygotic development will also be analyzed with both biochemical and genetic probes. The basic information obtained from this highly effective model system will eventually be utilized to investigate a mammalian system in which extra-nuclear inheritance and nucleus-organelle interactions have been implicated in developmental abnormality.